"Making major changes to the genetic code has so far been almost impossible. Now two research groups are presenting a breakthrough.
Gene scissors such as Crispr-Cas are considered the most modern tools for making genetic changes in plants, for example. This can quickly make them more tolerant to diseases or environmental stress, or improve their yields. "Genome editing" is also important in research, whether to understand diseases or develop drugs. In Germany, genome editing has so far only been approved for use in the laboratory, but in other countries, plants modified in this way are already being grown in fields. Crispr-Cas is considered a major research success, and the two developers of the process, Jennifer Doudna and Emmanuelle Charpentier, received the Nobel Prize for Chemistry in 2020.
Another instrument that is already being used for genome editing is so-called RNA interference. Small RNA molecules are introduced into cells that inhibit the conversion of genetic information into proteins by preventing the formation of messenger RNA (mRNA) or blocking its reading.
Addition to the toolbox
Both mechanisms, gene scissors and RNA interference, are mechanisms that occur naturally in cells so that the reading of genetic information works as accurately as possible. Scientists have researched them and learned how to use them to rewrite genetic codes. They have become important tools for green genetic engineering, but also in the development of medicines.
In nature, however, it is not only small changes to the genetic code in which these two mechanisms play a role. There is also often a rearrangement of larger areas of the genome. In this case, a large section of the genetic alphabet is inserted into existing genetic codes at once, and the corresponding changes can be extensive.
Bridges between DNA strands
Such rearrangements, known as insertion, inversion and deletion, are normally carried out by the cell with the help of certain enzymes: recombinases catalyze the breakage and recombination of DNA, transposases move DNA sections from one place to another. Scientists had observed and researched these rearrangement processes - but had not yet found a way to use the cellular tools required for this.
Now two working groups seem to have achieved exactly this: the teams led by Patrick Hsu from the Arc Institute and the University of California in Berkeley and by Hiroshi Nishimasu from the University of Tokyo describe in two publications in "Nature" how they managed to use so-called bridge RNA to change larger pieces of the genome at once than was possible with previous gene scissors.
"This is a completely new mechanism for biological programming," said Patrick Hsu at a press conference ahead of the publication. "We can use it to combine any DNA sequence we want." The researchers can make large-scale changes by inserting sequences at a location of their choice, reversing them or deleting them.
This new method does not cause a break in the DNA strand, the researchers emphasize. This is a disadvantage of gene scissors, which means that repair mechanisms have to be activated in the cell, which in turn can be prone to errors.
The key feature of the new method is the bridge RNA molecule. This is a piece of non-coding RNA (i.e. a single-stranded nuclease) that can be coded in such a way that it specifically contains two loops: one that allows it to pair with nucleic bases of the target DNA - and a second that connects with the "donor" DNA. Both the target and donor binding loops can be reprogrammed independently of each other.
In this way, a specific new combination (recombination) between two DNA molecules can be made possible. The advantage: Even long DNA sequences can be rearranged. "The bridge system offers a unified mechanism for the three basic DNA rearrangements required for genome design," says Patrick Hsu." [1]
1. Neues Werkzeug für die Gentechnik. Frankfurter Allgemeine Zeitung (online) Frankfurter Allgemeine Zeitung GmbH. Jun 26, 2024. Von Pia Heinemann
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